In WO 2005/092877 glucopyranosyl-substituted benzene derivatives of the general formula
wherein the groups R1 to R6 and R7a, R7b, R7c are as defined therein, are described. Such compounds have a valuable inhibitory effect on the sodium-dependent glucose cotransporter SGLT, particularly SGLT2.
In WO 2006/117359 a crystalline form of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-benzene and its synthesis is described.
In WO 2006/120208 several methods of synthesis of compounds of the formula
wherein R1 denotes cyclobutyl, cyclopentyl, cyclohexyl, R-tetrahydrofuran-3-yl, S-tetrahydrofuran-3-yl or tetrahydropyran-4-yl are described. The example XVIII therein relates to the synthesis of 1-chloro-4-(β-D-glucopyranos-1-yl)-2-(4-(S)-tetrahydrofuran-3-yloxy-benzyl)-benzene. According to the variant E therein (S)-3-[4-(5-iodo-2-chloro-benzyl)-phenoxy]-tetrahydrofuran is reacted with i-PrMgCl/LiCl in THF at low temperatures to form an organometallic intermediate. In an aqueous quenching step an aqueous NH4Cl solution (25 weight-%) is added. After the addition of methyl-tertbutylether the organic layer comprising the intermediate product is separated. In attempts to upscale this process it was observed that the separation of the aqueous and the organic phase may cause difficulties, for example by the formation of three phases.